Clostridium perfringens is an anaerobic, ubiquitous bacterium commonly found in soil, water and the intestine of mammals and birds. It is likely the best-known and most common anaerobic pathogen throughout the world (Songer, 1996).
Clostridium perfringens was first identified as a cause of human food poisoning-associated enteritis in the 1940s (McClung, 1945). Later, C. perfringens infection associated with enteritis necroticans was recognized after World War II in Germany. Various different strains of C. perfringens have been shown to cause significant diseases in domestic animals, particularly in food animals (Songer, 1996). These diseases include enteric syndromes such as avian necrotic enteritis, lamb dysentery, neonatal haemorrhagic or necrotizing enteritis in calves, foals and piglets, and ovine, caprine and bovine enterotoxemia. Type A C. perfringens has been associated with hemorrhagic gastroenteritis in dogs, as well as severe hemorrhagic and necrotizing enteritis in other animal species (Songer, 1996).
Clostridium perfringens as an Enteric Pathogen
Clostridium perfringens can produce both major and minor toxins. The pathogenesis of C. perfringens enteric diseases is directly associated with the toxins and enzymes that it produces. Clostridium perfringens strains are currently classified into five toxinotypes (types A-E) based on the major toxin production profile. The recent discoveries of new toxins in Type A C. perfringens, notably NetB and TpeL, as well as the association of the CPE enterotoxin with specific diseases suggest that further work is required to understand the diversity and variety of enteric disease caused by this bacterium.
NetB is a newly discovered toxin associated with necrotic enteritis of chickens. Studies have shown that this toxin has limited amino acid sequence similarity to the beta toxin in C. perfringens and the alpha toxin in Staphylococcus aureus (Keyburn et al., 2008). A recent study has shown that netB and 36 additional genes are present on a large plasmid-borne pathogenicity locus (Lepp et al., 2010).
Plasmids are an important way that C. perfringens acquires and develops novel toxins and other virulence-associated genes while adapting to different hosts and environments. The extraordinary adaptation of C. perfringens as a rapidly multiplying “flesh-eater” means that it commonly uses necrotizing toxins as an essential part of its virulence, and these are plasmid-based. Characterizing the plasmids from serious but poorly characterized type A infections in animals is a key to understanding the basis of virulence, and is required for development of control measures (Lepp et al. 2010; Parreira et al. 2012).
Clostridium perfringens and Severe Enterocolitis of Foals and Adult Horses
Typhlocolitis (inflammation of the caecum and colon) is an acute and severe disease of horses associated with high mortality, despite therapeutic interventions. Although progress has been made in identifying the causes of acute typhlocolitis in horses, some 60% of cases in horses have no known cause (Ruby et al., 2009; Mehdizadeh et al. 2013).
A number of authors have investigated the role of C. perfringens including Clostridium perfringens enterotoxin (CPE) in foals, since mild or moderate diarrhea is quite common in these animals. In 1990, Kanoe and colleagues isolated C. perfringens from all of the foals with enteric disease as well as in 13.8% of healthy foals; 55% of foals with enteric disease were positive for CPE. Netherwood and others (1996) also found that C. perfringens was significantly associated with foal diarrhea.
There is considerable work done on the role of type C C. perfringens in neonatal enterocolitis of foals (Traub-Dargatz and Jones, 1993; East et al., 1998; East et al. 2000; Diab et al. 2012), since it is associated with high mortality. Haemorrhagic, necrotizing enteritis of foals has also been described associated with type A C. perfringens, and has many similarities clinically or pathologically to type C associated infection (East et al. 1998; Timoney et al., 2005; Hazlett et al., 2011; Potter, 2011). In foals, the disease associated with both type A and type C C. perfringens is characteristically a necrotizing infection of the small intestine, particularly of the jejunum. The type A isolates usually possess the cpb2 and cpe genes. The basis of necrotizing enteritis associated with type A C. perfringens in foals is not understood, but it is a significant problem in foal rearing such that immunization of mares with C. perfringens culture supernatants containing the CPB2 toxin to try to prevent it through lactogenic immunity is sometimes practiced (Timoney et al., 2005). This commonly fatal type A C. perfringens-associated disease of foals is present in Ontario (Hazlett et al. 2011).
Clostridium perfringens and Canine Hemorrhagic Gastroenteritis
Clostridium perfringens type A-associated diarrhea and enteric disease in dogs is not well characterized, but may range in severity from mild and self-limiting to fatal acute hemorrhagic diarrhea (Marks, 2012). Understanding of the role of C. perfringens in diarrheal illness in dogs is incomplete, and the spectrum of disease attributed to the organism varies greatly. Its significance as a cause of diarrhea in dogs has been described as “controversial” (Gobeli et al., 2012). There has been an association of diarrheal illness with expression of the cpe enterotoxin gene, although the gene itself may be found in up to 14% of isolates of C. perfringens from healthy dogs (Marks, 2012). No gold standard exists for diagnosis (Marks, 2012). Hemorrhagic gastroenteritis is a syndrome characterized by sudden onset of vomiting with production of profuse bloody diarrhea, and is observed especially in small house dogs aged between 2 and 4 years (Marks, 2012). Its pathogenesis is unknown but has been attributed to C. perfringens enterotoxin (cpe) production (Marks, 2012). Hemorrhagic gastroenteritis associated with C. perfringens type A infection in dogs is characterized by the severe inflammation of the gastrointestinal tract, hemorrhage and rapid death (Prescott et al., 1978; Sasaki et al., 1999; Schelegel et al., 2012a). The presence of large numbers of clostridia-like bacilli, identified as C. perfringens, adhering to mucosal surfaces is a striking finding common in cases of fatal hemorrhagic gastroenteritis. Anecdotally, acute canine hemorrhagic gastroenteritis is a syndrome that is commonly recognized by veterinarians in small breed dogs and that may respond to rapid institution of antimicrobial and supportive treatments.
Type A C. perfringens has also been associated with gas gangrene and gastrointestinal diseases in humans; and enterotoxemia in cattle and lambs (Songer, 1996).